AzTrials
AzTrials

Locally Advanced or Metastatic EGFRm Non-small Cell Lung Cancer (NSCLC)Phase 2NCT07058519

A Study of Osimertinib-based Adaptive Treatment Guided by ctDNA EGFRm+ Monitoring in NSCLC

A Phase 2 study testing Osimertinib-based adaptive treatment and Osimertinib 80 MG in people with Locally Advanced or Metastatic EGFRm Non-small Cell Lung Cancer (NSCLC), run by Shanghai Chest Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The goal of this adaptive, interventional study is to assess the efficacy and safety of osimertinib-based adaptive treatment based on ctDNA dynamic monitoring in locally advanced or metastatic EGFRm NSCLC participants with ctDNA EGFRm clearance after osimertinib plus chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Osimertinib-based adaptive treatment and Osimertinib 80 MG
Could I receive a placebo?
No, everyone receives an active treatment
How many people
250 participants
Where
1 siteChina
Study dates
23 Sep 2025to 24 Jan 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of signed and dated, written informed consent form (ICF) prior to any study specific procedures.
  • Male or female participants aged 18 years old and above.
  • ECOG PS of 0-1.
  • Life expectancy of at least 3 months at recruitment.
  • Participants able to collect plasma samples at baseline.
  • Newly diagnosed, and histologically documented locally advanced or metastatic non-squamous NSCLC with sensitizing EGFR mutations positive (either Exon 19 deletion or 21 L858R, confirmed by histology or cytology), and classified as stage IIIB, IIIC, IV or recurrent NSCLC which are not amenable to curative surgery or radiotherapy (per Version 8 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology).
Show all 30Show fewer
  • Detectable EGFRm (Ex19del or L858R) in plasma ctDNA by central Super ARMS PCR testing at the time of screening.
  • Participants must have untreated advanced NSCLC and intend to receive osimertinib plus chemotherapy as first-line treatment. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior to receiving the first dose of study treatment.
  • Participants with asymptomatic and stable central nervous system (CNS) metastases for at least 2 weeks (for those who received definitive therapy and steroids, a stable neurological status for at least 2 weeks after completion of the treatment is required) will be allowed, including leptomeningeal metastases.
  • At least 1 lesion, not previously irradiated that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis of ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and as long as it has not been biopsied within 14 days of the baseline tumour assessment scans.
  • Patients with hepatitis B virus (HBV) are only eligible for inclusion if they meet all the following criteria:
  • Demonstrated absence of hepatitis C virus (HCV) co-infection or history of HCV co-infection
  • Demonstrated absence of human immunodeficiency virus (HIV) infection
  • Participants with active HBV infection are eligible if they are:
  • Receiving anti-viral treatment for at least 6 weeks prior to study treatment, HBV DNA is suppressed to <100 IU/mL and transaminase levels are below upper limit of normal (ULN).
  • Participants with a resolved or chronic HBV infection are eligible if they are:
  • Negative for hepatitis B surface antigen (HBsAg) and positive for hepatitis B core antibody [anti-HBc IgG or total anti-HBc Ab]. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment.
  • or
  • Positive for HBsAg, but for > 6 months have had transaminases levels below ULN and HBV DNA levels below <100 IU/mL or below the detectable limit of locally available test kit (i.e., are in an inactive carrier state). In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment.
  • Patients with HIV are only eligible for inclusion if they meet all the following criteria:
  • Demonstrated absence of HBV/ HCV co-infection
  • Undetectable viral RNA load for 6 months
  • CD4+ count of >350 cells/μL
  • No history of AIDS-defining opportunistic infection within the past 12 months
  • Stable for at least 4 weeks on the same anti-HIV medications
  • Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged 50 years or more and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments.
  • Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution.
  • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
  • Male participants must be willing to use barrier contraception.

Who cannot join

  • Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
  • Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the protocol, or active infection (e.g. participants receiving treatment for infection) including hepatitis C and HIV, or active uncontrolled HBV infection. Screening for chronic conditions is not required.
  • Any of the following cardiac criteria:
  • Mean resting corrected QTc >470 msec, obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value.
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block and second degree heart block.
  • Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including:
Show all 32Show fewer
  • Serum/plasma magnesium* < LLN
  • Serum/plasma calcium* < LLN
  • Hypokalaemia* ≥ CTCAE Grade 2 heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes.
  • Correction of electrolyte abnormalities should be documented prior to first dose
  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  • Absolute neutrophil count (ANC) <1.5 × 109/L
  • Platelet count <100 × 109/L
  • Hemoglobin <90 g/L
  • Alanine aminotransferase (ALT) >2.5 times the ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases.
  • Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases.
  • Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases.
  • Serum Creatinine >1.5 times ULN concurrent with creatinine clearance <50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN.
  • Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of investigational product (IP).
  • Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2 prior platinum-therapy related neuropathy.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
  • Prior treatment with any systemic anti-cancer therapy for advanced NSCLC not amenable to curative surgery or radiation including chemotherapy, biologic therapy, immunotherapy, or any investigational drug. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapies, investigational agents are permitted as long as treatment was completed at least 12 months prior to the development of recurrent disease.
  • Prior treatment with an EGFR-TKI.
  • Major surgery within 4 weeks of the first dose of IP. Procedures such as placement of vascular access, biopsy via mediastinoscopy or biopsy via video assisted thoracoscopic surgery (VATS) are permitted.
  • Palliative radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP.
  • Participants currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of cytochrome P450 (CYP) 3A4 (at least 3-week prior). All participants must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
  • Participation in another clinical study with an investigational product within 5 half-lives of the compound or 3 months whichever is greater prior to Day 1.
  • History of hypersensitivity to active or inactive excipients of Osimertinib or drugs with a similar chemical structure or class to Osimertinib.
  • Contraindication for pemetrexed and cisplatin/carboplatin according to local approved label.
  • Women who are breast-feeding.
  • Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
  • Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Shun Lu, PhD contact

86-21-6282199

shunlu@sjtu.edu.cn

China1 site, 1 recruiting

  • Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University

    Shanghai, Shanghai Municipality, 200030

    Shun Lu, PhD, 86-21-6282199, shunlu@sjtu.edu.cn

    Recruiting

Other trials in China

About this study

Official title: The Efficacy and Safety of Osimertinib-based Adaptive Treatment Guided by Circulating Tumour DNA (ctDNA) Epidermal Growth Factor Receptor Mutation-positive (EGFRm) Dynamic Monitoring in Locally Advanced or Metastatic EGFRm Non-small Cell Lung Cancer (NSCLC) Participants With ctDNA EGFRm Clearance After First-line Osimertinib Plus Chemotherapy: A Phase II, Multicentre, Prospective Study (Adaptive)

The goal of this adaptive, interventional study is to assess the efficacy and safety of osimertinib-based adaptive treatment based on ctDNA dynamic monitoring in locally advanced or metastatic EGFRm NSCLC participants with ctDNA EGFRm clearance after osimertinib plus chemotherapy. The main questions it aims to answer are: 1) PFS during adaptive treatment period in Cohort 1 defined as from initiation of Osimertinib in adaptive period to progression per investigator assessment; 2) Time from initiation of osimertinib in adaptive period to first ctDNA EGFRm relapse or death

Read the detailed description

Locally advanced or metastatic EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC) (Stage IIIB, IIIC, IV, or recurrent) has a poor prognosis. The 5-year survival rate for metastatic disease is only 8.9%.

While combination therapy with osimertinib and platinum-pemetrexed chemotherapy, as validated by the FLAURA2 trial, has demonstrated improved progression-free survival (PFS), it also introduces increased toxicity, treatment burden, and reduced quality of life. Notably, a subset of patients-approximately 25-30%-achieves long-term benefit from osimertinib monotherapy alone, highlighting the potential to personalize treatment intensity.

Emerging evidence supports circulating tumor DNA (ctDNA) as a dynamic biomarker for guiding therapy. Analyses from FLAURA2 and other studies have shown that early ctDNA EGFRm clearance strongly correlates with superior PFS and can identify patients who may not require continuous combination therapy. Adaptive strategies based on ctDNA clearance have enabled treatment de-escalation in early-stage and advanced NSCLC settings, maintaining efficacy while reducing toxicity. This trial builds on that rationale, aiming to validate ctDNA-guided adaptive therapy to balance efficacy, safety, and quality of life in EGFRm NSCLC.

Being tested
Osimertinib-based adaptive treatment, Osimertinib 80 MG
Keywords
NSCLC, EGFRm+, Osimertinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Osimertinib-based adaptive treatmentDrug

    Participants in Cohort 1 will receive Osimertinib-based adaptive treatment (either Osimertinib monotherapy or Osimertinib plus chemotherapy) depending on ctDNA EGFRm clearance or relapse by ctDNA EGFRm dynamic monitoring, until radiological disease progression (PD) as per RECIST v1.1 or other withdrawal criteria are met.

  • Osimertinib 80 MGDrug

    Participants in Cohort 2 will receive Osimertinib 80 mg once daily (QD) plus pemetrexed maintenance every 3 weeks (Q3W) until radiological PD as per RECIST v1.1 or other withdrawal criteria are met.

Study groups in NCT07058519
Study groupRoleWhat they receive
Cohort 1 (EGFRm ctDNA Clearance Group)ExperimentalEGFRm ctDNA Clearance Group
Receives: Drug: Osimertinib-based adaptive treatment
Cohort 2 (ctDNA EGFRm non-clearance group)ExperimentalNot described
Receives: Drug: Osimertinib 80 MG

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival (PFS) in Cohort 1

    Progression-Free Survival (PFS) is defined as the time from the first dose of osimertinib during the adaptive treatment period to the first documentation of disease progression based on investigator assessment according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or death from any cause, whichever occurs first.

    Measured: From initiation of osimertinib in the adaptive therapy period until radiological disease progression or death (up to 33 months).

  2. Time to First ctDNA EGFRm Relapse or Death in Cohort 1

    Time to ctDNA EGFR mutation-positive (EGFRm) relapse is defined as the time from the start of osimertinib treatment in the adaptive therapy period to the first detection of EGFRm in plasma circulating tumour DNA (ctDNA), as assessed by Super ARMS PCR, or death from any cause, whichever occurs first.

    Measured: From initiation of osimertinib in the adaptive therapy period until ctDNA EGFR mutation relapse or death (up to 33 months)

Secondary outcomes (6)

  1. Overall Survival (OS) in Cohort 1

    Overall Survival (OS) is defined as the time from the first dose of osimertinib in the adaptive therapy period to death from any cause. The 24-month landmark survival rate will be reported.

    Measured: From initiation of osimertinib in adaptive therapy period until death (up to 33 months)

  2. Cumulative Duration of Chemotherapy Holiday in Cohort 1

    The cumulative duration (in weeks) that participants in Cohort 1 receive osimertinib monotherapy without chemotherapy will be calculated during the adaptive treatment period.

    Measured: From start of adaptive therapy to disease progression or death (up to 33 months)

  3. Progression-Free Survival (PFS) in Cohort 2

    PFS in Cohort 2 is defined as the time from the start of osimertinib plus pemetrexed maintenance therapy to the first documentation of disease progression per RECIST v1.1 or death from any cause.

    Measured: From initiation of maintenance therapy to radiological disease progression or death (up to 33 months)

  4. Overall Survival (OS) in Cohort 2

    OS is defined as the time from the first dose of osimertinib plus pemetrexed maintenance therapy to death from any cause. The 24-month landmark survival rate will be reported.

    Measured: From initiation of maintenance therapy to death (up to 33 months)

  5. Change from Baseline in Health-Related Quality of Life Scores (EORTC QLQ-C30)

    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) (0-100) will be used to evaluate participants' health-related quality of life. Higher scores on the QLQ-C30 indicate bad life quality of patient. Change from baseline in domain scores will be analyzed. The higher the score is, the worse the quality of life is.

    Measured: From baseline through end of treatment (up to 33 months)

  6. Change from Baseline in Lung Cancer-Specific Symptoms (EORTC QLQ-LC13)

    The EORTC QLQ-LC13 questionnaire will be used to assess lung cancer-specific symptoms (e.g., cough, dyspnea), with score range 0-100. Higher scores on the QLQ-LC13 indicate worse symptom severity. Changes from baseline will be reported.

    Measured: From baseline through end of treatment (up to 33 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jul 2025
  2. Study start23 Sep 2025
  3. Primary completion24 Jan 2029 (estimated)
  4. Study completion24 Jan 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
250 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07058519
Sponsor's protocol ID
ESR-24-22779
Status last verified
Sep 2025
First submitted
16 Jun 2025
Last updated
26 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Osimertinib-based adaptive treatment and Osimertinib 80 MG in people with Locally Advanced or Metastatic EGFRm Non-small Cell Lung Cancer (NSCLC), run by Shanghai Chest Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Shun Lu, PhD (86-21-6282199, shunlu@sjtu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) in Cohort 1 (time frame: From initiation of osimertinib in the adaptive therapy period until radiological disease progression or death (up to 33 months).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07058519.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in